Submissions for variant NM_001370466.1(NOD2):c.1036C>T (p.Arg346Cys)

gnomAD frequency: 0.00021  dbSNP: rs145293873

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002513891	SCV000935827	likely benign	Blau syndrome; Regional enteritis	2023-12-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001753488	SCV001987702	uncertain significance	not provided	2020-11-06	criteria provided, single submitter	clinical testing	Identified in an individual with Crohn disease and an individual with spondylarthropathy, however, segregation information was not included (Lesage et al., 2002; Miceli-Richard et al., 2002); Functional studies indicate that this variant does not affect NF-kB activation, however, further studies are warranted (Tanabe et al., 2004); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11385576, 31784737, 11875755, 15044951, 12115249)
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262685	SCV002543016	likely benign	Autoinflammatory syndrome	2021-05-14	criteria provided, single submitter	clinical testing
Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital	RCV001753488	SCV002775021	uncertain significance	not provided	2022-12-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001753488	SCV004139313	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	NOD2: BP4
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001753488	SCV004562960	uncertain significance	not provided	2023-01-25	criteria provided, single submitter	clinical testing	The NOD2 c.1117C>T; p.Arg373Cys variant (rs145293873), to our knowledge, is not reported in individuals with Blau syndrome, but is reported in the literature in individuals affected with Crohn’s disease, spondyloarthropathy, or dermatitis (Lesage 2002, Miceli-Richard 2002, Taylan 2015). This variant is also reported in ClinVar (Variation ID: 97902) and is found in the general population with an overall allele frequency of 0.0184% (52/282,834 alleles) in the Genome Aggregation Database. In vitro functional analyses demonstrate wild-type function is retained (Tanabe 2004). Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.231). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Lesage S et al. CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. Am J Hum Genet. 2002 Apr;70(4):845-57. PMID: 11875755. Miceli-Richard C et al. CARD15/NOD2 analyses in spondylarthropathy. Arthritis Rheum. 2002 May;46(5):1405-6. PMID: 12115249. Tanabe T et al. Regulatory regions and critical residues of NOD2 involved in muramyl dipeptide recognition. EMBO J. 2004 Apr 7;23(7):1587-97. PMID: 15044951. Taylan F et al. Whole-exome sequencing of Ethiopian patients with ichthyosis vulgaris and atopic dermatitis. J Allergy Clin Immunol. 2015 Aug;136(2):507-9.e19. PMID: 25819062.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier	RCV000084160	SCV000116291	not provided	Blau syndrome		no assertion provided	not provided
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001753488	SCV002034296	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001753488	SCV002037688	uncertain significance	not provided		no assertion criteria provided	clinical testing